- Total synthesis of leukotrienes from butadiene
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The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA4 methyl ester (4), LTC4 (1), LTD4 (2) and LTE4 (3), as well as (14S, 15S)-LTA4 methyl ester (24) and the novel [2H2]-LTA4 methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB4.
- Rodriguez, Ana,Nomen, Miguel,Spur, Bernd W.,Godfroid, Jean-Jacques,Lee, Tak H.
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p. 2991 - 3000
(2007/10/03)
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- Stereochemistry and Mechanism of the Biosynthesis of Leukotriene A4 from 5(S)-Hydroperoxy-6(E),8,11,14(Z)-eicosatetraenoic Acid. Evidence for an Organoiron Intermediate
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The pathway of biosynthesis of leukotriene A4 (LTA4, 2) from 5(S)-hydroperoxy-6(E),8,11,14(Z)-eicosatetraenoic acid (5-S-HPETE, 1) has been explored by the comparative study of (S)- and (R)-lipoxygenase (LO) enzymes as catalysts.The purified LO from potato, an S-lipoxygenase, converts (anaerobically) 1 to 2 (determined as the characteristic hydrolysis mixture of two epimeric 5,6-diols and two epimeric 5,12-diols), as previously reported by Samuelsson et al.However, the 8-R-LO from the coral Plexaura homomalla transforms 1 (anaerobically) into 6-epi-LTA4 (6).Theobserved divergence of stereopathways agrees with predictions based on the intermediacy of organoiron intermediates in enzymic lipoxygenation (Scheme I) and detailed in Schemes II and III.Further evidence for the intervention of such intermediates has been obtained by trapping experiments under pure O2 at pressures of 1-60 atm.Under O2 pressure 1 is converted by the potato LO to a new product, the bis(hydroperoxide) 7, whereas the coral LO converts 1 to the diastereomeric bis(hydroperoxide) 9.
- Corey, E. J.,Wright, Stephen W.,Matsuda, Seiichi P. T.
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p. 1452 - 1455
(2007/10/02)
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- SYNTHESIS OF TETRADEUTERATED LTA4 METHYL ESTER
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Progress in GC/MS coupling in the field of lipids prompted us to prepare deuterated leukotrienes as stable standard compounds.Thus, chiral -tetradeuterated LTA4 methyl ester 4b was synthesized by reduction of the appropriate diyne precursor and will lead to the corresponding tetradeuterated peptidoleukotrienes.
- Lellouche, J. P.,Aubert, F.,Beaucourt, J. P.
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p. 3069 - 3072
(2007/10/02)
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- A FACILE STEREOSELECTIVE SYNTHESIS OF LEUKOTRIENE A4(LTA4) METHYL ESTER
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A facile synthesis of LTA4 1 methyl ester was achieved according to Scheme 1, in which the key intermediate 6 and 7 were prepared with the new procedures conveniently, stereoselectively and in good yields.
- Wang, Yanfang,Li, Jincui,Wu, Yulin,Huang, Yaozeng,Shi, Lilan,Yang, Jianhua
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p. 4583 - 4584
(2007/10/02)
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- AN EFFICIENT AND SIMPLE METHOD THE CONVERSION OF 15-HPETE TO 14,15-EPETE (LIPOTRIENE A) AND 5-HPETE TO LEUKOTRIENE A AS THE METHYL ESTERS
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Simple new methodology is described for the synthesis from arachidonic acid of the important eicosanoids lipotriene A methyl ester (5) and leukotriene A methyl ester (10), a key feature being the use of a novel chemical method for effecting the allylic hydroperoxide oxiranyl carbinol rearrangement.
- Corey, E. J.,Su, Wei-guo,Mehrotra, Mukund M.
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p. 5123 - 5126
(2007/10/02)
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- Enantiospecific syntheses of leukotrienes C4, D4 and E4 and [14,15-3H2]leukotriene E4 dimethyl ester
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A 'chiral-pool' approach was employed to synthesize various leukotrienes (slow-reacting substance of anaphylaxis, SRS-A) enantiospecifically. The pivotal (S,S)-trans-epoxy alcohol 9 was prepared by efficient and facile routes starting from erythorbic acid (D-araboascorbic acid, 13). This epoxide could also be produced starting from D-glucose. The epimeric (S,R)-cis-epoxide 38 was obtained utilizing L-tartaric acid as the chiral starting material. Elaboration of 9 into leukotriene A4 methyl ester (5) and the potassium salts of leukotrienes C4 (4a), D4 (4b), and E4 (4c) was accomplished by standard methods. These salts exhibited potent contractile activities in the in vitro guinea pig ileum assay. Reduction of 14,15-dehydroleukotriene A4 methyl ester (44) with tritium gas gave [14,15-3H2]-5 and subsequently the dimethyl ester of [14,15-3H2]leukotriene E4 having a high specific activity of 40 Ci/mmol.
- Cohen,Banner,Lopresti,et al.
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p. 3661 - 3672
(2007/10/02)
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- SYNTHESIS OF THE 7-CIS ISOMER OF THE NATURAL LEUKOTRIENE D4
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Methyl 5(S),6(S)-oxido-11-oxo-7-cis-9-trans-undecadienoate 5 was prepared and used for the synthesis of the novel 7-cis-LTD4 (9) as well as, after isomerization to the all-trans dienal ester 3, for that of the natural leukotrienes.
- Ernest, I.,Main, A. J.,Menasse, R.
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p. 167 - 170
(2007/10/02)
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- CHEMICAL CONVERSION OF ARACHIDONIC ACID TO SLOW REACTING SUBSTANCES
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The synthesis of slow reacting substances, leukotrienes C, D, and E, can be accomplished conveniently by a stereoselective biomimetic route.Details are provided for the conversion of 5-HPETE methyl ester 4 to leukotriene methyl ester (2) and thence to leukotrienes C and D.
- Corey, E. J.,Barton, Alan E.
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p. 2351 - 2354
(2007/10/02)
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- A NOVEL STEREOSPECIFIC SYNTHESIS OF (+/-)-LEUKOTRIENE A4(LTA4),METHYL ESTER
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The reaction of the phosphonate 1 with the epoxyaldehyde 2 is reported as the key step in a novel stereospecific synthesis of (+/-)-LTA4, methyl ester 3.
- Buck, Judith C.,Ellis, Frank,North, Peter, C.
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p. 4161 - 4162
(2007/10/02)
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- Process for the preparation of esters of leukotriene A
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Esters of leukotriene A are conveniently prepared by reacting 9-oxo-5,6-trans-epoxynon-7(E)-enoates with 11-triphenylphosphoranylidene undec-6(Z),9(Z)-diene. Esters of leukotriene-A are useful intermediates in the synthesis of naturally occurring leukotrienes, which have been shown to be potent broncho-constricting substances. Novel intermediates to the esters of leukotriene A, 9-oxo-5,6-transepoxynon-7(E)-enoates and 7-oxo-5,6-transepoxyheptanoates, are disclosed.
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- THE STEREOSPECIFIC SYNTHESIS OF LEUKOTRIENE A4 (LTA4), 5-EPI-LTA4, 6-EPI-LTA4 AND 5-EPI,6-EPI-LTA4
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The stereospecific synthesis of the four isomers of 6-formyl-5,6-epoxy hexanoic acid methyl ester 8, 15, 23, 30 from 2-deoxy-D-ribose have allowed the preperation of methyl esters of LTA4, 1, and its three unnatural isomers.
- Rokach, Joshua,Zamboni, Robert,Lau, Cheuk-Kun,Guindon, Yvan
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p. 2759 - 2762
(2007/10/02)
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- Total synthesis of slow reacting substances (SRS). "Leukotriene C-2" (11-trans-leukotriene C) (3) and leukotriene D (4)
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Syntheses are described for the "slow reacting substances" 11-trans-leukotriene C (3) (previously known as leukotriene C-2) and leukotriene D (4), the cys-gly analog of leukotriene C (2). The synthesized leukotrienes 3 and 4 were instrumental in the assignment of structure to these members of the family of naturally occuring slow reacting substances which includes also 2.
- Corey,Clark, David A.,Marfat, Anthony,Goto, Giichi
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p. 3143 - 3146
(2007/10/02)
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- CONVERGENT SYNTHESIS OF LEUKOTRIENE A METHYL ESTER
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A convergent total synthesis of methyl 5,6-oxido-6,9,11,14-eicosapentaenoate from oct-2-yn-1-ol and methyl 4-formylbutyrate is described.
- Gleason, John G.,Bryan, D. Boles,Kinzig, Charles M.
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p. 1129 - 1132
(2007/10/02)
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- SYNTHESIS, SEPARATION AND N.M.R. SPECTRA OF THREE DOUBLE BOND ISOMERS OF LEUKOTRIENE A METHYL ESTER
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The synthesis and h.p.l.c. separation of three double bond isomers of leukotriene A methyl ester is described, their stereochemistry being assigned by 1H N.M.R.
- Baker, S. Richard,Jamieson, William B.,McKey, Stuart W.,Morgan, Sarah E.,Rackham, David M.,et al.
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p. 4123 - 4126
(2007/10/02)
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